This project has the following objectives: l) Induction of genital cancer in rat offspring by transplacental and transmammary exposure to diethylstilbestrol (DES); 2) Investigation of natural estrogens (estrogens, estradiol, estriol) in regard to potential transplacental carcinogenesis; 3) Elucidation of the mechanism(s) by which estrogenic substances (DES, natural estrogens) influence development and differentiation of the urogenital apparatus of the rat embryo and fetus; 4) Investigation of the relatinship of disturbance in transformation of columnar Mullerian epithelium into squamous epithelium and subsequent development of vaginal and cervical cancer; 5) Determination of usefulness of the pregnant rat as a screening model for substances potentially carcinogenic and teratogenic to human offspring. The following procedures will be applied to reach the objectives outlined above: a) Subcutaneous injection of DES and natural estrogens to pregnant rats during the embryonic and fetal stage of gestation; b) Documentation of DES distribution in embryo and fetal tissues by maternal administration of radiolabelled DES; c) Transmammary exposure of suckling offspring by subcutaneous injection of DES into lactating mother rats; d) Measurement of DES excretion into milk by administration of radiolabelled DES to lactating rats; e) Life-long observation of exposed offspring with regard to body weight, vaginal smear cytology, vaginal biopsy, and surgical exploration; f) Histopathological examinaion of tissues of the genital tract and of putative neoplastic changes in other tissues.